Genome of Mycobacterium Documented :

Several great lives lost with Tuberculosis :

The 22 countries shown on the map accounts for 80% of the TB cases in the worldStop TB Partnership :

The 22 countries shown on the map accounts for 80% of the TB cases in the worldStop TB Partnership

Distribution of Tuberculosis :

Distribution of Tuberculosis TB is present worldwide The largest numbers of cases occur in the regions of south-east Asia and sub-Saharan Africa, reaching 700 cases per 100,000 individuals in some areas. The highest mortality is in the Africa region, owing to the synergy with HIV. Strains that are resistant to a single drug have been documented in every country surveyed.

Transmission is dependent on closeness and time of contact :

Transmission is dependent on closeness and time of contact In penitentiary care contacts are very close and prolonged – culture positive cases can also transmit TB especially to HIV positive population

Basic facts on Pulmonary Tuberculosis :

Basic facts on Pulmonary Tuberculosis Chronic disease
Recurrent infections
Transmissible
Inflammatory Bacterial infection with tissue damage
Most common involvement of lungs
Nodular scars and cavities on the apex of one or both lungs
Spontaneous pneumo -thorax and pleural effusions.
Can also lead to disseminated infection in several organs.

Pulmonary Tuberculosis a Major Public health concern :

Pulmonary Tuberculosis a Major Public health concern

Smear positive are highly infectious :

Smear positive are highly infectious Pulmonary cavitary cases are usually smear positive
Immediate isolation is necessary until proven conversion
HIV positive are more often smear negative pulmonary or extra pulmonary cases – should they be isolated
Culturing is needed in smear negative cases.

Signs and symptoms :

Signs and symptoms Early symptoms
Common cold symptoms
Listlessness, fatigue, fever, a minimally productive cough of yellow or green sputum and a general feeling of malaise.
Later symptoms
Night sweats, fever, cough with purulent secretions and haemoptysis, dyspnoea, chest pain, and hoarseness appear.

Diagnosis by X-ray :

Diagnosis by X-ray Chest x-rays: Multi nodular infiltrate above or behind the clavicle with or without pleural effusion unilaterally or bilaterally.

Diagnosis Sputum investigation :

Diagnosis Sputum investigation Cultures will reveal the presence of mycobacterium tuberculosis
Patients stay infectious for as long as the bacilli are excreted in the sputum

What are the current primary challenges in TB? :

What are the current primary challenges in TB? Non-adherence to therapy
Escalating levels of drug-resistance
Co-administration of anti-retroviral therapy

Definition of drug resistance :

Definition of drug resistance Drug resistance in mycobacteria is defined as a decrease in sensitivity to a sufficient degree to be reasonably certain that the strain concerned is different from a sample of wild strains of human type that have never come in contact with the drugs

Mechanisims of Drug Resistance in Tuberculosis :

Mechanisims of Drug Resistance in Tuberculosis

Several Drugs becoming resistant :

Several Drugs becoming resistant

Development of Drug Resistancefrom the perspective of the patient: :

Development of Drug Resistancefrom the perspective of the patient: The presence of drug resistant strains results from simple Darwinian pressures, brought out by the presence of antibiotics
Multiple drug resistant strains result from the step-wise accumulation of individual resistance elements therefore MDR-TB is MAN-MADE

Types of drug resistance :

Types of drug resistance Drug resistance in TB may be broadly classified as primary or acquired. When drug resistance is demonstrated in a patient who has never received anti-TB treatment previously, it is termed primary resitance

Drug Resistance in TB :

Drug Resistance in TB When to suspect drug resistance?
Persistent sputum positivity
Fall and rise phenomenon of sputum AFB
Clinical or radiological deterioration in the presence of positive sputum
Provided patient has been regular in drug intake

The careful monitoring of patients with drug resistant TB is essential to their safe and successful completion of therapy * :

The careful monitoring of patients with drug resistant TB is essential to their safe and successful completion of therapy * Monitoring of patients with drug resistant TB includes
Initial evaluation
General monitoring
Clinical response monitoring
Bacteriological response
Drug side effects monitoring
To monitor adherence to treatment

Monitoring Inpatient vs. ambulatory facilities * :

Monitoring Inpatient vs. ambulatory facilities * Hospitalized patients are monitored at least daily by physicians and other medical personnel
Outpatient are monitored:
5-7 times per week by staff dispensing DOT
By physician:
Every week or every other week early in the course
Monthly after things are going very well
Occasionally less frequently in second year of treatment
By nursing staff, social workers, consultants as it needed

Monitoring Inpatient vs. ambulatory facilities* :

Monitoring Inpatient vs. ambulatory facilities* Hospitalized patients are monitored at least daily by physicians and other medical personnel
Outpatient are monitored:
5-7 times per week by staff dispensing DOT
By physician:
Every week or every other week early in the course
Monthly after things are going very well
Occasionally less frequently in second year of treatment
By nursing staff, social workers, consultants as it needed

Pre-treatment screening and evaluation* :

Pre-treatment screening and evaluation* The initial evaluation may identify patients who are at risk for adverse effects
The monitoring of treatment and the adverse effects may have to be more intensive in patients with pre-existing conditions or conditions identified at the initial evaluation.

Screening by DOT worker* :

Screening by DOT worker* At every DOT encounter:
Conversation with patient about possible side effects or another problems
Ensuring that patient take their medications daily as prescribed
Patients should be observed swallowing each dose of medication
Standard medical record-keeping
Perform frequent patient visits, collect data, and triage significant findings to physicians

Sputum smear and culture* :

Sputum smear and culture* At least monthly until conversion
Only real sputum can be evaluated (not saliva) Use of sputum induction techniques when needed 2 cultures can be used, in case of contamination
Specimens for monitoring do not need to be done in duplicate, but doing so can increase sensitivity of the monitoring
If the patient remains smear and/or culture positive at the end of 4 months of treatment, or the patient again becomes smear/culture positive after having been previously negative, DST should repeat to decide further treatment possibilities

Chest x- ray. * :

Chest x- ray. * At baseline
Every 3 month until conversion
Then every 6 month
Also:
If consider surgical intervention
Necessity of repeat chest x-ray examination will depend on the patient’s clinical condition that warrants re-examination (i.e. deterioration of health condition, rule out other diseases)
Never accept MDR-TB or a Failure based only on X-ray examination criteria

Validation of DOT* :

Validation of DOT* Cant be underestimated, Most important part of monitoring
Record all necessary information on the treatment card and the patient card
Ask the patient how he is. Are his symptoms improving? Has he had any problems
Valid DOT
Give all tablets and observe the patient taking his medicines and ask him to return the next day.
Patients observed swallowing of each dose, Check mouth
Examine the patient for side effects like: Nausea, headache, jaundice, anaemia, dry itchy skin, and other complications etc.

WorldHealth Organization (WHO) and the InternationalUnion Against Tuberculosis and Lung Diseases :

WorldHealth Organization (WHO) and the InternationalUnion Against Tuberculosis and Lung Diseases WHO and other agencies replaced the term primary resistance by the term “drug resistance among new cases” and acquired resistance by the term “drug resistance among previously treated cases

Current Scientific Documentations on Drug Resistance in Tuberculosis :

The Much Discussed Article on XDR TB in the Lancet* :

The Much Discussed Article on XDR TB in the Lancet* Of the 221 multi-drug resistant (MDR-TB) cases, 53 (24%) were XDR.
Almost all (52 of 53) of the XDR-TB patients died, with a median survival of only 16 days from the time of diagnosis (in the 42 patients with confirmed dates of death)
All the 44 XDR TB patients who were tested for HIV were found co-infected
55% patents had never received anti-TB drugs, suggesting primary transmission of XDR pathogen
67% patients had been admitted to the hospital in the preceding 2 years, suggesting potential role of nosocomial transmission. * Gandhi et al. Lancet 2006;368:1575-80.

Impact of Drug Resistance :

Impact of Drug Resistance

How x-MDR generated :

How x-MDR generated Acquired resistance is that which occurs as a result of specific previous treatment. The level of primary resistance in the community is considered to reflect the efficacy of control measures in the past, while the level of acquired resistance is a measure of on-going TB control measures

Several reasons identified for resistance :

Several reasons identified for resistance iv) improper prescription of regimens; (v) interruption of chemotherapy due to side effects; (vi) non-adherence of patients to the prescribed drug therapy; (vii) availability of anti-TB drugs across the counter, without prescription;

Several reasons identified for resistance :

Several reasons identified for resistance viii) massive bacillary load; (ix) illiteracy and low socio-economic status of the patients; (x) the epidemic of HIV infection; (xi) laboratory delays in identification and susceptibility testing of M. tuberculosis isolates; (xii) use of non standardized laboratory techniques, poor quality drug powders and lack of quality control measures; and (xiii) use of anti-TB drugs for indications other than tuberculosis

Several reasons identified for resistance :

Several reasons identified for resistance DR-TB raises concerns of a future TB epidemic with restricted treatment options, and jeopardizes the major gains made in TB control and progress on reducing TB deaths among people living with HIV/AIDS. It is therefore vital that TB control is managed properly and new tools developed to prevent, treat and diagnose the disease.

Definition of Multidrug resistant Tuberculosis :

Definition of Multidrug resistant Tuberculosis Multi-drug resistant tuberculosis is defined as resistance to isoniazid and Rifampicin whether there is resistance to other drugs or not. It is therefore incorrect, by this definition, to classify a patient has having multi-drug resistant disease if they have an infection with a bacterium susceptible to Rifampicin but resistant to many other drugs

Mechanism and transmission of drug resistance :

Mechanism and transmission of drug resistance Drug resistance in M. tuberculosis occurs by random, single step, spontaneous mutation at a low but predictable frequency, in large bacterial populations. The probability of incidence of drug resistant mutants is 10-8 for Rifampicin, while for isoniazid and some of the other commonly used drugs

Poor mangement of infected lead to grwoing resistance :

Poor mangement of infected lead to grwoing resistance Resistance to anti-TB drugs in populations is a phenomenon that occurs primarily due to poorly managed TB care. Problems include incorrect drug prescribing practices by providers, poor quality drugs or erratic supply of drugs, and also patient non-adherence

XDR-TB :

XDR-TB The description of XDR-TB was first used earlier in 2006, following a joint survey by WHO and the US Centres for Disease Control and Prevention (CDC)

What is XDR-TB? :

What is XDR-TB? MDR-TB (Multidrug Resistant TB) describes strains of tuberculosis that are resistant to at least the two main first-line TB drugs - isoniazid and rifampicin. XDR-TB, or Extensive Drug Resistant TB (also referred to as Extreme Drug Resistance) is MDR-TB that is also resistant to three or more of the six classes of second-line drugs.

Extreme Drug resistant Tuberculosis (XDR-TB) :

Extreme Drug resistant Tuberculosis (XDR-TB) Resistant to all first line drugs namely; Isoniazid and Rifampin and Three or more second line drugs (SLD’S) that are used to treat MDR-TB
Thequinalones like Ofloaxin
Or
Aminoglycosides like Capreomycin & Kanamycin
No third-line drugs available to treat XDR-TB since none has been developed in the last 40 years.

Background Extensively drug-resistant tuberculosis :

Background Extensively drug-resistant tuberculosis Extensively drug-resistant tuberculosis has been reported in 45 countries, including countries with limited resources and a high burden of tuberculosis.

Transmissionof X -MDR :

Transmissionof X -MDR Like other forms of TB, XDR-TB is spread through the air. When a person with infectious TB coughs, sneezes, talks or spits, they propel Mycobacterium into the air.

Best options to diagnoseX-MDR tuberculosis :

Best options to diagnoseX-MDR tuberculosis Successful diagnosis of XDR-TB depends on the patient’s access to quality health-care services. If TB bacteria are found in the sputum, the diagnosis of TB can be made in a day or two, but this finding will not be able to distinguish between drug-susceptible and drug-resistant TB. To evaluate drug susceptibility, the bacteria need to be cultivated and tested in a suitable laboratory. Final diagnosis in this way for TB, and especially for XDR-TB, may take from 6 to 16 weeks To reduce the time needed for diagnosis, new tools for rapid TB diagnosis are urgently needed.

When to suspect MDR TB ? :

When to suspect MDR TB ? Patients not showing any reduction in bacillary population after 3-months of regular treatment with Cat II regimen
Sputum positive patients who are contacts of a known MDR TB patient

How to evaluate MDR TB ? :

How to evaluate MDR TB ? MDR TB is only a laboratory proved HR resistance
Clinical suspicion should be followed by lab. Confirmation
Laboratories should be quality controlled TRC

Extreme Drug resistant Tuberculosis (XDR-TB) and AIDS :

Extreme Drug resistant Tuberculosis (XDR-TB) and AIDS It can also be contracted without a patient receiving any previous treatment for TB
Mostly associated with HIV positive patients
People infected with HIV are particularly susceptible as their immune systems are already weakened.
HIV has the potential to fast tracking XDR-TB into an uncontrollable epidemic
Average survival period for patients infected with XDR-TB is 16 days.

World Health Organisation (WHO) Guidelines for treatment of MDR-TB :

World Health Organisation (WHO) Guidelines for treatment of MDR-TB Strengthen basic TB care to prevent the emergence of drug-resistance
Ensure prompt diagnosis and treatment of drug resistant cases to cure existing cases and prevent further transmission
Increase collaboration between HIV and TB control programmes to provide necessary prevention and care to co-infected patients
Increase investment in laboratory infrastructures to enable better detection and management of resistant cases.

When to evaluate for MDR TB ? :

When to evaluate for MDR TB ? Patients not showing any reduction in bacillary population after 3-months of regular treatment with Cat II regimen
Sputum positive patients who are contacts of a known MDR TB patient

Seven point action plan. SAMRC, USA,CDC, WHO :

Seven point action plan. SAMRC, USA,CDC, WHO Conduct rapid surveys to detect cases of XDR-TB
Enhance laboratory capacity for detection of drug resistance
Improve technical capacity of clinical and public health managers to effectively respond to XDR-TB outbreaks
Implement infection control precautions, especially in facilities where HIV-positive individuals are receiving care
Increase research support for anti-TB drug development
Increase research support for rapid diagnostic test development
Promote universal access to antiretroviral drugs under joint TB-HIV activities

The basis of anti-TB therapy and MDR-TB: HDL -- a comprehensive approach and unified system of care :

THE NEW MDR-TB Guidelines :

THE NEW MDR-TB Guidelines A flexible framework approach combining both clinical and programmatic aspects of DOTS Plus based on essential programme conditions
But encouraging programs to tailor their case-finding and treatment strategies to the local epidemiological and Programme situation
Reflect GLC expert consensus and evidence and experience from GLC projects thus far

Changing Drug Regimes :

Changing Drug Regimes

DOTS-Plus :

DOTS-Plus A comprehensive strategy of the WHO Stop TB Partnership, developed by the DOTS-Plus Working Group, for the diagnosis and management of MDR-TB and other forms of drug resistant TB

Mainstreaming DOTS-Plus into DOTS :

Mainstreaming DOTS-Plus into DOTS Referral from DOTS-programme: failures, chronics
Same (reference) laboratory
Same treatment delivery system
Drug-procurement and R&R: adapted but integrated!

Parameters to consider when designing a DOTS-Plus strategy :

Parameters to consider when designing a DOTS-Plus strategy Government and NTP commitment
Well performing basic DOTS
Program is able to implement the 5 components of DOTS-Plus
Rational case-finding strategy using quality assured smear, culture and DST ( concordance with a SRL)
Representative DRS data for rational country/area-specific treatment design and planning of procurement
Reliable DOT throughout treatment
Free effective side-effect management
Regular supply of ALL drugs involved!

Global Project coverage 2005 :

IMPACT OF HIV ON TB :

IMPACT OF HIV ON TB Nearly 8% of the global TB is attributable to HIV
One third increase in TB in last five years is attributable to HIV
Health services struggle to cope with the large and rising numbers of TB patients.
TB accelerates the progression to AIDS
TB shortens the survival of patients with HIV infection
TB is the cause of death for one out of three people with AIDS worldwide

Patterns of HIV-related TB :

Patterns of HIV-related TB Early HIV
Similar to Non HIV patients in both Adults and Children
Late HIV
More of Extra-pulmonary TB when compared to TB patients without HIV infection
Weight loss and fever are more common in HIV-positive PTB patients than in those who are HIV-negative.
Cough and Haemoptysis are less common in HIV-positive PTB patients than in those who are HIV-negative
Physical signs
Non-specific may present as atypical cases.

Patterns of HIV-related TBPulmonary TB :

Patterns of HIV-related TBPulmonary TB

TB in HIV patients - Diagnosis :

TB in HIV patients - Diagnosis Sputum Microscopy:
Continue to be a Gold standard diagnosis of TB even in high HIV-prevalence areas
Chest X-Ray:
in persons suspected of having TB who are sputum smear-negative and who do not respond to 2 weeks of antibiotic therapy
When only one sample is positive
Suspected complications, like Pneumothroax or other opportunistic infections.

TB in HIV patients – DiagnosisOther investigations :

TB in HIV patients – DiagnosisOther investigations Tuberculin test
does not measure immunity.
does not indicate the presence or extent of TB disease
“Cut off” for positive reaction? Is reduced to 5 mm
Mycobacterial Culture
Takes 8-12 weeks
Not readily available
Only reference labs take up quality control to identify atypical Mycobacterium essential

TB in HIV patients Extra-pulmonary TB :

TB in HIV patients Extra-pulmonary TB Reported in up to 70% of HIV-related TB cases when the CD4 lymphocyte count is less than 100.
Main types seen are –
Lymphadenopathy (peripheral, mediastinal, abdominal)
Pleural / pericardial effusion
Organ involvement especially liver, spleen and meningeal involvement

TB in HIV patients Pediatric TB :

TB in HIV patients Pediatric TB Duration of illness greater than 4 weeks, particularly if the illness has not responded to other treatments, e.g. broad-spectrum antibiotics for persistent cough;
evidence of wasting (i.e. under 60% of median weight-for-age), especially if there is a lack of weight gain in response to intensive nutritional support;
family history of sputum-positive PTB (this is very important information)
significant or “positive” tuberculin test.

TB in HIV patients Pediatric TB :

MDR TB and HIV :

MDR TB and HIV MDR TB occurs with the same frequency in HIV patients as in TB patients who are smear negative
Transmission of drug-resistant strains among HIV-infected patients in congregate settings occurs leading to ‘outbreaks’ of MDR TB in such settings
Infection control measures absolutely essential in settings where large number of HIV TB patients stay together.

Universal guidelines for prevention of Tuberculosis :

Universal guidelines for prevention of Tuberculosis

Prevention of transmission - Simple measures more effective :

Prevention of transmission - Simple measures more effective Early diagnosis and treatment
Isolation of different patient categories
Cure of most of TB cases
However Unknown TB cases are major source of transmission

Effective laboratory Diagnosis :

X-ray continues to be a minimal need in Diagnosis of TB :

X-ray continues to be a minimal need in Diagnosis of TB Screening at entry, prior to transfer (?) and by symptoms
In risk groups half yearly during stay in penitentiary care
HIV positive are more often smear negative – early dg needs x-ray
In case of lack of equipment cooperation with other units or civilian society (mobile units?)

A WORLD FREE OF TB :

A WORLD FREE OF TB WHO is working to dramatically reduce the burden of TB, and halve TB deaths and prevalence by 2015, through its Stop TB Strategy and supporting the Global Plan to Stop TB.